S iah2‐deficient mice show impaired skin wound repair

Hypoxia is associated with the dermal wound healing process and hypoxia signaling is presumed to be crucial for normal wound repair. The S iah2 ubiquitin ligase controls the abundance of hypoxia‐inducible factor‐1 alpha, and loss of S iah2 results in destabilization of hypoxia‐inducible factor‐1 alpha under hypoxia. Utilizing S iah2 −/− mice we demonstrate that cutaneous wound healing is impaired in these mice. Wounds in S iah2 −/− mice heal slower and are associated with delayed induction of myofibroblast infiltration and reduced collagen deposition. This coincides with delayed angiogenesis and reduced macrophage infiltration into the wounds of S iah2 −/− mice. We furthermore demonstrate that primary S iah2 −/− dermal fibroblasts have reduced migratory capacities and produce less collagen than wild‐type fibroblasts. Additionally, S iah2 −/− fibroblasts showed conserved responses to transforming growth factor‐β at the receptor level (p S mad 2 C activation) but reduced responses downstream. Together, our data show, for the first time, that S iah2 is involved as a positive regulator in the wound healing response. Understanding the role of hypoxia signaling in tissue repair and fibrosis and interference with the hypoxia signaling pathway via regulation of S iah2 may provide new targets for clinical regulation of fibrosis and scarring.